Antibacterial agents of the quinolonecarboxylic acid class have achieved a striking progress in recent years. Because of broad antibacterial spectrum and potent bactericidal activity ranging from Gram-positive bacteria to negative bacteria, they have become to be used for surgical infectious diseases as well as urinary tract infectious disease and their usefulness is highly appreciated, leading to great contribution in the clinical practice.
1-Cyclopropyl-6-fluoro-1,4-dihydro-8-methoxy-7-(3-methyl-1-piperazinyl)-4-o xo-3-quinolinecarboxylic acid is particularly noted because of not only its potent antibacterial activity but also higher selectivity against bacteria from mammalian cells, which brings on an excellent selective toxicity.
In Japanese Unexamined Patent Publication No. Sho 62-252772, hemihydrate of 1-cyclopropyl-6-fluoro-1,4-dihydro-8-methoxy-7-(3-methyl-1-piperazinyl)-4- oxo-3-quinolinecarboxylic acid represented by a formula (2) is disclosed. ##STR2##
1-Cyclopropyl-6-fluoro-1,4-dihydro-8-methoxy-7-(3-methyl-1-piperazinyl)-4-o xo-3-quinolinecarboxylic acid tends to make a hydrate because of its strong hygroscopicity, and it easily forms a hemihydrate when recrystallizing from water-containing organic solvent or when drying crystals obtained by the recrystallization method by neutralization according to acid-alkali recrystallization.
It was revealed by us, however, that the measured weight of this hemihydrate increases with the rise of environmental humidity. It was further revealed by us that the tablet containing the hemihydrate has poor disintegration and dissolution rates, leading to disadvantages in pharmaceutical manufacturing.
Moreover, in Japanese Unexamined Patent Publication No. Sho 63-198664, hydrochloride of 1-cyclopropyl-6-fluoro-1,4-dihydro-8-methoxy-7-(3-methyl-1-piperazinyl)-4- oxo-3-quinolinecarboxylic acid represented by a formula (3) is disclosed. ##STR3##
However, with respect to this hydrochloride (3), too, the instability due to the hygroscopicity of drug substance same as or more than that of hemihydrate (2) and the problems of poor disintegration and dissolution rate when converted to tablets have become evident.